扶正化瘀胶囊联用熊去氧胆酸治疗原发性胆汁性肝硬化的近期疗效观察及护理

目的探讨扶正化瘀胶囊联合熊去氧胆酸治疗原发性胆汁性肝硬化(PBC)的疗效。方法 130例PBC患者随机分为观察组与对照组各65例,常规护肝及对症支持治疗基础上,对照组单用熊去氧胆酸治疗,观察组加用扶正化瘀胶囊,疗程24周。结果治疗后两组患者肝功能指标均显著改善,观察组各项指标降低幅度较对照组更为明显(P<0.01);观察组完全反应率84.6%明显高于对照组63.1%(P<0.01)。结论扶正化瘀胶囊联用熊去氧胆酸治疗PBC疗效确切,安全性好。     

中等剂量熊去氧胆酸治疗原发性胆汁性肝硬化的疗效研究

目的研究分析中等剂量熊去氧胆酸治疗原发性胆汁性肝硬化的治疗效果。方法对2008年1月至2011年12月期间在我院接受治疗的原发性胆汁性肝硬化患者进行临床资料的回顾性分析,将120例患者按在入院顺序随机分为两组,对照组60例,采用思美泰治疗,实验组60例采用熊去氧胆酸中等剂量治疗。观察患者的肝功能改善状况,分析治疗效果。结果两组患者在用药治疗后,肢体乏力、皮肤瘙痒等症状均得到明显的改善,较之治疗前具有明显差异,差异具有统计学意义,(P<0.05),且观察组患者的治疗效果优于对照组,差异具有统计学意义,(P<0.05)。结论中等剂量熊去氧胆酸治疗原发性胆汁性肝硬化具有较好的临床效果,值得临床推广使用。     

原发性胆汁性肝硬化临床验治40例分析

目的观察熊去氧胆酸治疗原发性胆汁性肝硬化的临床疗效。方法 40例原发性胆汁性肝硬化患者,抗线粒体抗体（AMA）和抗线粒体抗体-M2（AMA-M2）均阳性,经熊去氧胆酸持续治疗时间0.5～5（平均1.8）a,观察临床表现,肝功能生化指标血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、白蛋白（Alb）、总胆红素（TBil）、碱性磷酸酶（AKP）和r-谷氨酰转酞酶（r-GT）等变化。结果所有患者经熊去氧胆酸治疗后,临床症状明显改善,肝功能ALT、AST、TBil、AKP和r-GT明显下降（均P〈0.01）,Alb升高（P〈0.01）。患者在治疗中无明显药物不良反应和死亡发生。结论熊去氧胆酸长期治疗原发性胆汁性肝硬化,能有效减轻和控制症状,改善肝功能生化指标,减缓病情进展。     

熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化疗效观察

目的观察熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化（PBC）的临床疗效。方法将32例原发性胆汁性肝硬化患者随机分为治疗组和对照组,治疗组给予熊去氧胆酸联合复方甘草酸苷治疗,对照组单用熊去氧胆酸治疗,疗程4～6周,观察两组的疗效及不良反应情况。结果两组患者治疗后肝功能相关生化指标及临床疗效较治疗前均有改善,且治疗组优于对照组（P〈0.05）,两组均无严重不良反应发生。结论熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化疗效显著,安全有效。     

熊去氧胆酸联合异甘草酸镁治疗原发性胆汁性肝硬化的近期疗效观察及护理

目的观察熊去氧胆酸联合异甘草酸镁治疗原发性胆汁性肝硬化的近期疗效．探讨原发性胆汁性肝硬化护理方案。方法将18例原发性胆汁性肝硬化患者随机分为两组。治疗组11例,予熊去氧胆酸联合异甘草酸镁治疗;对照组7侧．单纯予熊去氧胆酸治疗。疗程均为4周．治疗结束后观察：丙氨酸氨基转氨酶（ALT）,总胆红素（TBIL）．碱性磷酸酶（ALP）,谷氨酰转肽酶（GGT）。结果治疗组患者治疗后肝功能各项指标均明显改善。并且治疗后TBIL和ALT与对照组比较也有显著性差异,而对照组仅GGT有显著下降。结论熊去氧胆酸联合异甘草酸镁的治疗方案加上良好的护理对原发性胆汁性肝硬化有较理想的近期教泉     

熊去氧胆酸联合复方甘草酸苷对原发性胆汁性肝硬化的疗效分析

目的:对熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化的疗效进行评价。方法:将2010年1月—2012年12月52例原发性胆汁性肝硬化患者随机分组:试验组给予熊去氧胆酸联合复方甘草酸苷治疗,总疗程为4周;对照组仅给予复方甘草酸苷治疗,疗程相同。观察两组临床症状缓解状况及生化指标改变情况。结果:两组患者治疗前后临床症状及生化指标均有不同程度改变,但试验组明显优于对照组(P<0.05)。结论:熊去氧胆酸联合复方甘草酸苷治疗原发性胆汁性肝硬化疗效确切。     

熊去氧胆酸治疗原发性胆汁性肝硬化82例肝功酶谱变化观察

目的观察熊去氧胆酸胶囊治疗原发性胆汁性肝硬化患者的早期疗效。方法 82例患者均给予甘草酸二铵保肝基础治疗的同时口服熊去氧胆酸胶囊每日13～15mg/kg。结果 8周后肝功酶谱ALT、AST、GGT、ALP、TBA较治疗前明显下降,前后均数比较P<0.05,具有统计学意义。结论熊去氧胆酸胶囊治疗原发性胆汁性肝硬化患者能够早期、快速改善肝脏生化学指标。     

腺苷蛋氨酸联合前列地尔治疗原发性胆汁性肝硬化的疗效观察

目的对比观察在使用传统熊去氧胆酸胶囊基础上联合腺苷蛋氨酸及前列地尔治疗原发性胆汁性肝硬化的疗效。方法将40例原发性胆汁性肝硬化患者随机分为2组,每纽20例。对照组给予熊去氧胆酸胶囊0．25g每天3次口服,共3个月。治疗组在上述基础上给予每天静滴腺苷蛋氨酸针1g联合前列地尔针20IU治疗,共10d,每月一次,共3次。结果随访3个月,按肝功能改善情况评分,治疗组优良率为82．68％,对照组优良率为65．12％,经统计分析,P〈0．05。结论腺苷蛋氨酸联合前列地尔对原发性胆汁性肝硬化的治疗可比传统单用熊去氧胆酸胶囊治疗取得更为良好的疗效。     

熊去氧胆酸联合通胆汤对原发性胆汁性肝硬化的治疗作用

目的探究熊去氧胆酸联合通胆汤对原发性胆汁性肝硬化治疗作用。方法观察组给予基础治疗、熊去氧胆酸(UDCA)和通胆汤治疗;对照组给予基础治疗、熊去氧胆酸(UDCA)。结果对观察组行熊去氧胆酸(UDCA)联合通胆汤治疗,治疗12周其完全反应率为83.3%,较对照组53.3%,有显著差异,P<0.05。结论熊去氧胆酸(UDCA)能够有效缓解早中期的PBC患者的病情,若加用通胆汤,能够加速完全反应时间,使之更好地改善临床症状,提高患者生活质量,具有积极的临床意义。     

熊去氧胆酸治疗早产儿静脉营养相关性胆汁淤积症的临床疗效

目的探讨熊去氧胆酸治疗早产儿静脉营养相关性胆汁淤积症的临床疗效。方法选取福建医科大学附属泉州第一医院2017年10月—2018年9月收治的静脉营养相关性胆汁淤积症早产儿76例,按照随机数字表法分为对照组与观察组,各38例。对照组予以常规治疗,观察组在对照组基础上予以熊去氧胆酸治疗,两组均连续治疗2个疗程。比较两组临床疗效,治疗前后肝功能指标〔总胆红素(TBiL)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)〕、血清内毒素水平,并观察两组不良反应发生情况。结果观察组临床疗效优于对照组(P<0.05)。治疗前两组TBiL、AST、ALT比较,差异无统计学意义(P>0.05);治疗后观察组TBiL、AST、ALT低于对照组(P<0.05)。治疗前两组血清内毒素水平比较,差异无统计学意义(P>0.05);治疗后观察组血清内毒素水平低于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论熊去氧胆酸治疗早产儿静脉营养相关性胆汁淤积症的临床疗效确切,可有效改善早产儿肝功能,且安全性较高。     

Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy

BACKGROUND: Ursodeoxycholic acid is widely used as the standard therapy for the treatment of primary biliary cirrhosis and other cholestatic liver diseases. Although it has been shown to improve biochemical markers and delay disease progression, its effect upon fatigue and pruritus, is at best uncertain. AIM: To assess the safety and efficacy of methotrexate for treating symptomatic primary biliary cirrhosis patients who were biochemical partial responders or non-responders to ursodeoxycholic acid therapy. METHODS: We treated eight consecutive primary biliary cirrhosis patients with methotrexate who were followed in a single hepatology clinical practice, who were symptomatic, and who had had an incomplete biochemical response to ursodeoxycholic acid therapy. Pruritus and fatigue were assessed at each clinic visit and graded from 0 (asymptomatic) to 4 (incapacitating). RESULTS: The median dose of methotrexate was 13.75 mg/week (range 7.5-15) and the mean duration of methotrexate therapy was 49 months (range 11-126). At the end of follow-up pruritus in six of seven patients had improved, and fatigue in all patients had improved with the addition of methotrexate therapy (pruritus: baseline 2.9 +/- 1.1 vs. end of treatment 0.6 +/- 1.5, P < or = 0.0175, and fatigue: baseline 3.0 +/- 0.8, vs. end of treatment 1.0 +/- 0.8, P < or = 0.0023). Improvement in symptoms was associated with a significant improvement in biochemical markers of cholestasis. No significant adverse effects of methotrexate were documented. CONCLUSIONS: Methotrexate should be considered as a potential additive treatment for symptomatic primary biliary cirrhosis patients who are incomplete biochemical responders to ursodeoxycholic acid therapy.     

Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis

AIM: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL. METHODS: A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3 years of follow-up. Patients with cirrhosis underwent endoscopy every 12 months. In a sub-group of patients without cirrhosis, who consented, liver biopsy was repeated at the end of the study. RESULTS: The number of treatment failures (i.e. dead, orthotopic liver transplantation (OLT), complications of cirrhosis, doubling of bilirubin, untreatable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of improvement of liver enzymes related to cholestasis and cytolysis and of amelioration of pruritus. The Mayo score values increased less above the baseline values at 24 and 36 month-intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre-cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C group, whereas no changes in these histological scores were observed in the UDCA group. CONCLUSIONS: The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but significant reduction of disease progress.     

Pharmacological treatment of biliary cirrhosis with ursodeoxycholic acid

Importance of the field: Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indication for liver transplantation. Treatment with ursodeoxycholic acid has clearly improved the natural history of primary biliary cirrhosis.

Areas covered in this review: The treatment of primary biliary cirrhosis with a focus on ursodeoxycholic acid is covered. Papers related to treatment of primary biliary cirrhosis and associated conditions, using a variety of drugs but with a focus on ursodeoxycholic acid, are included. The papers reviewed date from 1984 – 2009.

What will the reader gain: The reader will gain an up-to-date understanding of current treatment strategies for primary biliary cirrhosis using ursodeoxycholic acid and an appreciation of what conditions are improved with this therapy and what associated conditions are not.

Take-home message: Ursodeoxycholic acid in a dose of 13 – 15 mg/kg/day should be considered in all patients with primary biliary cirrhosis who have abnormal liver enzymes.     

Ursodeoxycholic acid: a second look. Primary biliary cirrhosis: dashed hopes

(1) In 1996 the evidence, though limited, suggested that the hydrophilic bile acid ursodeoxycholic acid slowed the progression of primary biliary cirrhosis. Given the absence of an effective alternative, we considered that the treatment was "A real advance" in this setting. (2) The file is far bulkier now. A meta-analysis of 11 randomised placebo-controlled trials of ursodeoxycholic acid in the treatment of primary biliary cirrhosis did not show efficacy. Histologically, the data suggest that the drug lowers the risk of hepatic fibrosis, but this is based on a low level of evidence. Moreover, there was no clinical improvement in the longest randomised trial (median follow-up 3.4 years). (3) Likewise, ursodeoxycholic acid seems to have a biochemical effect but no clear clinical effect in sclerosing cholangitis or in treating the hepatic complications of cystic fibrosis. (4) The main adverse effects are gastrointestinal disorders. (5) There are still no drugs clearly capable of slowing the clinical progression of primary biliary cirrhosis. Nevertheless, given the minor adverse effects of ursodeoxycholic acid, some patients may wish to gamble on a possible benefit in the very long term. (6) When primary biliary cirrhosis becomes symptomatic (with encephalopathy, osteomalacia, etc.) pending liver transplantation, treatment is aimed at controlling symptoms and preventing the rupture of oesophageal varices.     

Is there an optimal therapeutic regimen for antimitochondrial antibody‐negative primary biliary cirrhosis (autoimmune cholangitis)?

Testing for antimitochondrial antibodies is the most useful laboratory procedure in the diagnosis of primary biliary cirrhosis; nevertheless, 5-10% of patients with typical features of primary biliary cirrhosis do not have detectable antimitochondrial antibodies, their condition being referred to as antimitochondrial antibody-negative primary biliary cirrhosis or "autoimmune cholangitis". Uncertainty exists whether antimitochondrial antibody-positive and -negative primary biliary cirrhosis represent distinct entities. We reviewed studies that compared: (i) the clinical, laboratory and histological characteristics of antimitochondrial antibody-positive and -negative primary biliary cirrhosis; (ii) the response to treatment of both conditions; and (iii) the response of autoimmune cholangitis to ursodeoxycholic acid and immunosuppressive therapy. Antimitochondrial antibody-positive and -negative primary biliary cirrhosis were characterized by similar clinical, laboratory and histological abnormalities, clinical course and survival. Antimitochondrial antibody status did not seem to affect the response to ursodeoxycholic acid. At present, the efficacy of therapies for autoimmune cholangitis has not been established in controlled trials. Of 52 patients with autoimmune cholangitis treated with ursodeoxycholic acid in 13 uncontrolled studies, 83% had serum biochemical improvement. Also, a favourable effect of immunosuppressive drugs occurred in 57% of 54 patients with autoimmune cholangitis in 17 uncontrolled studies. Each of these trials included very few patients and most evaluated the effects of treatment on surrogate markers of disease only. No marker that consistently distinguished patients who would respond favourably to ursodeoxycholic acid or immunosuppression was apparent. Consequently, treatment is, at present, empirical. However, ursodeoxycholic acid may be given when histology reveals bile duct lesions, whereas immunosuppressive therapy should probably be reserved for patients exhibiting interface hepatitis.     

Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study

Background: Results from animal studies and preliminary data from pilot studies in patients with primary biliary cirrhosis suggest that tauro-ursodeoxycholic acid has metabolic properties that may favour its long-term use as an alternative to ursodeoxycholic acid for patients with chronic cholestatic liver diseases. No direct comparison of tauro-ursodeoxycholic and ursodeoxycholic acids have yet been carried out in primary biliary cirrhosis.
Methods: The effects of ursodeoxycholic and tauro-ursodeoxycholic acids were compared in 23 patients with primary biliary cirrhosis according to a crossover design. Both drugs were administered at the daily dose of 500 mg, in a randomly assigned sequence for two 6-month periods separated by a 3-month wash-out period.
Results: Serum liver enzymes related to cholestasis and cytolysis consistently improved, as compared to baseline values, during the administration of both ursodeoxycholic and tauro-ursodeoxycholic acids, but no significant difference between these two bile acids was found. Both treatments were well tolerated and no patient complained of side effects.
Conclusion: In the short-term, tauro-ursodeoxycholic acid appears to be safe and at least as effective as ursodeoxycholic acid for the treatment of primary biliary cirrhosis.     

Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis

BACKGROUND: Endothelins and nitric oxide regulate sinusoidal blood flow and the perfusion of the peribiliary vascular plexus. AIMS: To study the serum and hepatic vein concentration of ET-1, ET-2, ET-3 and nitric oxide in patients with primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment. METHODS: Endothelins and nitrites/nitrates were measured in serum and hepatic vein blood in primary biliary cirrhosis and viral cirrhotic patients prior and after ursodeoxycholic acid therapy and in serum in controls. Endothelins were measured with commercial enzyme-linked immunosorbent assays and nitrites/nitrates with a modification of Griess reaction. RESULTS: The ET-1 and ET-3 levels were similar in patients and controls. Primary biliary cirrhosis patients had the highest serum ET-2 (P < 0.001) compared with other groups. Nitrites/nitrates was increased in primary biliary cirrhosis (P < 0.05) compared with normal. ET-2 and nitric oxide were similar in all primary biliary cirrhosis stages. Ursodeoxycholic acid significantly decreased ET-2 in all stages (I and II: P < 0.05 and III and IV: P < 0.01) and increased nitric oxide (P < 0.05) in early primary biliary cirrhosis. Hepatic vein ET-1 and ET-3 were higher in viral cirrhosis patients, but only in primary biliary cirrhosis a significant difference for ET-1 and ET-3 between hepatic and peripheral veins was found. CONCLUSIONS: Increased ET-2 is an early defect in primary biliary cirrhosis that is significantly reduced by the ursodeoxycholic acid treatment. The possibility of a more generalized endothelial cell dysfunction in primary biliary cirrhosis requires further investigation.     

Pharmacokinetics and bone effects of budesonide in primary biliary cirrhosis

BACKGROUND/AIM: To evaluate the safety of budesonide in primary biliary cirrhosis. METHODS: 77 primary biliary cirrhosis patients, with stages I-III at entry, were randomized to use either budesonide 6 mg and ursodeoxycholic acid 15 mg/kg (group A), or ursodeoxycholic acid alone (group B) daily for 3 years. In 22 patients, budesonide pharmacokinetics was determined after 3 years. Bone mass density was measured in 62 patients at baseline and 3 years; in 57 patients also liver biopsies were performed. RESULTS: At 3 years, no significant differences in the pharmacokinetics of budesonide were found between the patients with stages 0-I, II and III primary biliary cirrhosis. In group A, bone mass density in femoral neck and lumbar spine were decreased by 3.6% (P = 0.0002) and 2.8% (P = 0.003) from the baseline. In group B, the corresponding decreases were 1.9% (P = 0.029) and 0.7% (P = 0.25), but the differences between the groups were not statistically significant (P = 0.16 for femoral neck and P = 0.08 for lumbar spine). CONCLUSIONS: The plasma concentrations of budesonide do not significantly differ within stages I-III primary biliary cirrhosis patients. The combination of budesonide and ursodeoxycholic acid may decrease bone mass density in the femoral neck and lumbar spine in some primary biliary cirrhosis patients, and bone mass density is recommended to be monitored during budesonide therapy.     

Long-term ursodeoxycholic acid therapy for primary biliary cirrhosis: a follow-up to 12 years

BACKGROUND: It is uncertain whether ursodeoxycholic acid therapy slows down the progression of primary biliary cirrhosis, according to two meta-analyses. However, the randomized trials evaluated had only a median of 24 months of follow-up. AIM: To evaluate long-term ursodeoxycholic acid therapy in primary biliary cirrhosis. METHODS: We evaluated 209 consecutive primary biliary cirrhosis patients, 69 compliant with ursodeoxycholic acid and 140 untreated [mean follow-up 5.79 (s.d. = 4.73) and 4.87 (s.d. = 5.21) years, respectively] with onset of all complications documented. Comparison was made following adjustment for baseline differences according to Cox modelling, Mayo and Royal Free prognostic models. RESULTS: Bilirubin and alkaline phosphatase concentrations improved with ursodeoxycholic acid (at 36 months, P = 0.007 and 0.018, respectively). Unadjusted Kaplan-Meier analysis showed benefit (P = 0.028), as 44 (31%) untreated and 15 (22%) ursodeoxycholic acid patients died or had liver transplantation. However, there was no difference when adjusted by Cox modelling (P = 0.267), Mayo (P = 0.698) and Royal Free models (P = 0.559). New pruritus or fatigue or other complications were not different, either before or after adjustment for baseline characteristics. CONCLUSIONS: Long-term ursodeoxycholic acid therapy did not alter disease progression in primary biliary cirrhosis patients despite a significant improvement in serum bilirubin and alkaline phosphatase consistent with, and similar to, those seen in ursodeoxycholic acid cohorts in randomized trials.     

熊去氧胆酸联合丁二磺酸腺苷蛋氨酸治疗肝硬化黄疸的疗效观察

目的观察熊去氧胆酸胶囊（优思弗）联合丁二磺酸腺苷蛋氨酸（思美泰）治疗肝硬化黄疸的疗效。方法肝硬化黄疽患者共46例,治疗组（23例）用熊去氧胆酸胶囊[UDCA13．15mg/（kg·d）,口服,Bid或Tid]联合丁二磺酸腺苷蛋氨酸（思美泰1000mg／d,静脉滴注）治疗,不使用甘草酸制剂等保肝药;对照组应用丁二磺酸腺苷蛋氨酸,其余药物基本相同。疗程2周,观察临床症状、肝功能的变化。结果经治疗后两组患者临床症状均有明显改善,肝功能指标均有好转,治疗组TBi1下降更明显（P〈0．05）。结论熊去氧胆酸联合丁二磺酸腺苷蛋氨酸治疗肝硬化黄疸效果更好。